Table 3.

The potential strategies to overcome acquired resistance.

Clinical characteristics or resistance mechanisms	Potential strategies
Oligo-progression	Continuous ICB plus local therapy (132–136)
Neoantigen depletion	Oncolytic virotherapy such as T-VEC (137–141)
	Continuous ICB plus vaccine (142)
	Continuous ICB plus superantigens (143)
Defects in antigen presentation machinery	NK cell-based therapy (144)
	Continuous ICB plus RIG-I activation (145)
	Continuous ICB plus overexpression of NLRC5 or intratumoral delivery of BO-112 (146)
Aberrations of interferon signaling	T cell–based adoptive cell therapy (146)
Tumor-induced exclusion/immunosuppression	Continuous ICB plus inhibition of the involved pathways, including Wnt/β-catenin, PI3K-Akt, IFN-β/NOS2, CSF-1, TGF-β, adenosine, and IDO
	Continuous ICB plus microenvironment-targeting strategies (147)
Tumor cell plasticity	Continuous ICB plus epigenetic modulation (148, 149)
	Continuous ICB plus MRD-targeting strategies (150)
	Continuous ICB plus EMT inhibition
	Continuous ICB plus ferroptosis induction (151–153)
	Continuous ICB plus other plasticity-targeting strategies (107, 108)
Other immune checkpoints upregulation	Continuous ICB plus inhibition of the upregulating checkpoints
Other strategies	Continuous ICB plus chemotherapy, anti-angiogenesis therapy, radiotherapy, target therapy, or another immune checkpoint inhibitor
	Stop using ICB and to use later-line chemotherapy